ω-3多不饱和脂肪酸配方改善抑郁症患者认知功能损害的临床随机双盲对照试验

The formula ofω-3 polyunsaturated fatty acids improving cognitive impairment in patients with depression:a clinical randomized double-blind controlled trial

目的评价ω-3多不饱和脂肪酸(ω-3 polyunsaturated fatty acids,ω-3 PUFA)不同配比对抑郁症及其认知功能损害的辅助治疗效果。方法采用随机、双盲对照试验,纳入抑郁症患者后随机分配到改善认知组、改善抑郁组和安慰剂组。改善认知组每天服用1388 mg二十二碳六烯酸(docosahexaenoic acid,DHA)与692 mg二十碳五烯酸(eicosapentaenoicacid,EPA),改善抑郁组每天服用1248 mg EPA与832 mg DHA,安慰剂组服用相等剂量大豆油,连续治疗12周,期间维持精神科药物治疗。治疗6周和12周末,以24项汉密尔顿抑郁量表(Hamilton depression scale,HAMD-24)评价抑郁症状疗效,以标准化的精神分裂症认知功能成套测验——共识版(MATRICS consensus cognitive battery,MCCB)评价认知功能损害疗效。结果共纳入抑郁症患者46例,其中改善认知组22例、改善抑郁组12例、安慰剂组12例。最终改善认知组21例、改善抑郁组12例、安慰剂组10例完成至少1次随访并纳入分析。经6周治疗后,改善抑郁组(19.00±10.70)和改善认知组(16.58±9.39)的HAMD-24得分均低于安慰剂组(31.10±10.03),差异有统计学意义(P<0.01);而治疗12周后,仅改善抑郁组(13.58±8.43)低于安慰剂组(28.10±15.04),差异有统计学意义(P=0.02)。认知功能方面,经6周和12周治疗后,3组未发现任何维度的认知测评得分存在分组与时间交互效应(均P>0.05)。改善抑郁组(2例,16.7%)、改善认知组(0%)及安慰剂组(0%)的不良事件发生率没有统计学差异(P=0.13)。结论连续6周服用ω-3PUFA对抑郁症患者的抑郁症状有改善作用,其中EPA比例较高的配方作用较为明显,而两种不同比例的ω-3PUFA配方对认知功能均没有改善作用。

Objective To investigate the effects of different ratios ofω-3 polyunsaturated fatty acids(ω-3 PUFA)on depression and cognitive impairment in patients with major depression.Methods A randomized,double-blinded controlled trial was used to randomly assign patients with depression to a cognitive improvement group,a depression improvement group,and a placebo group.The cognitive improvement group took 1388 mg of docosahexaenoic acid(DHA)and 692 mg of eicosapentaenoic acid(EPA)every day and the depression improvement group took 1248 mg of EPA and 832 mg of DHA every day.The placebo group took the same dose of soybean oil for 12 weeks,during which psychiatric medication was maintained.The 24-item Hamilton depression scale(HAMD-24)was used to evaluate depressive symptoms,and the standardized MATRICS consensus cognitive battery(MCCB)was used to evaluate cognitive function after 6 weeks and 12 weeks,respectively.Results The study recruited a total of 46 patients with depression including 22 in the cognitive improvement group,12 in the depression improvement group,and 12 in the placebo group.After 6 weeks of treatment,the HAMD-24 scores were significantly lower in the depression improvement group(19.00±10.70)and cognitive improvement group(16.58±9.39)than in the placebo group(31.10±10.03)(P<0.01).After 12 weeks of treatment,HAMD-24 scores were significantly lower in the depression improvement group(13.58±8.43)than in the placebo group(28.10±15.04)(P=0.02).No significant interaction effect was found on the cognitive assessment scores in any dimension after 6 weeks and 12 weeks of treatment(P>0.05).The incidence rate of adverse events in the depression improvement group was 16.7%(2/12),and no adverse events were reported in the other two groups.There was no significant difference in the incidence of adverse events among the three groups(P=0.13).Conclusion Treatment withω-3PUFA for 6 weeks can improve the depressive symptoms of patients with depression.The formula with a higher ratio of EPA exhibits higher effectiveness while the two groups ofω-3PUFA formulas with different ratios do not improve cognitive function.